The somatostatinergic system in the mammalian cochlea

Vesna Radojevic,Yves Brand,Cristian Setz,Daniel Bodmer,Claudia Hanusek,Josef P Kapfhammer

doi:10.1186/1471-2202-12-89

Vesna Radojevic, Yves Brand + Show 4 more

Open Access

https://doi.org/10.1186/1471-2202-12-89

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Abstract

BackgroundLittle is known about expression and function of the somatostatinergic system in the mammalian cochlea. We have previously shown that somatostatin administration may have a protective effect on gentamicin-induced hair cell loss. In this study, we have analyzed the cochlear expression of somatostatin receptor 1 (SST1) and somatostatin receptor 2 (SST2) at both the mRNA and the protein level in wild-type mice, as well as in SST1 and SST2 knock-out (KO) mice and in cultivated neurosensory cells.ResultsWe demonstrate that the somatostatin receptors SST1 and SST2 are specifically expressed in outer and inner hair cells (HCs) of the organ of Corti (OC), as well as in defined supporting cells. The expression of SST1 and SST2 receptors in cultivated P5 mouse OC explants was similar to their expression in inner and outer hair cells. Somatostatin itself was not expressed in the mammalian cochlea, suggesting that somatostatin reaches its receptors either through the blood-labyrinthine barrier from the systemic circulation or via the endolymphatic duct from the endolymphatic sac. We used mice with a deletion of either SST1 or SST2 to learn more about the regulation of SST1 and SST2 receptor expression. We demonstrate that in SST1 KO mice, SST2 was expressed in outer HCs and Deiters' cells, but not in pillar cells or inner HCs, as compared with wild-type mice. In contrast, in SST2 KO mice, the expression pattern of the SST1 receptor was not altered relative to wild-type mice.ConclusionsThese findings reveal that somatostatin receptors demonstrate specific expression in HCs and supporting cells of the mouse cochlea, and that absence of SST1 alters the expression of SST2. This specific expression pattern suggests that somatostatin receptors may have important functional roles in the inner ear.

Highlights

Little is known about expression and function of the somatostatinergic system in the mammalian cochlea
The strongest immunoreactivity was observed in the apical part of the outer and inner hair cells (HCs) (Figure 2B), and weaker staining was present in the basal part of the HCs and the pillar cells
Double labeling with the neurofilament marker SMI31, which stains axons, revealed that the axons connecting the spiral ganglion (SG) with the OC do not express somatostatin receptor 1 (SST1) (Figure 2D) SST1 immunostaining was completely absent in the SST1 KO mice, confirming the specificity of the antibodies used (Figure 2C)

Summary

Introduction

Little is known about expression and function of the somatostatinergic system in the mammalian cochlea. We have analyzed the cochlear expression of somatostatin receptor 1 (SST1) and somatostatin receptor 2 (SST2) at both the mRNA and the protein level in wild-type mice, as well as in SST1 and SST2 knock-out (KO) mice and in cultivated neurosensory cells. Somatostatin acts via a family of G-proteincoupled receptors known as somatostatin receptors 1-5 (SST1 - SST5), which are differentially distributed throughout the CNS [2]. Signaling through somatostatin receptors is complex and involves auto-, para-, or Studies over the last few years in mice have shown that somatostatin and its receptors appear to play an important role in cell death. In a retina ischemia model, activation of the SST2 receptor protected retinal neurons from damage [10]. Studies in mice with genetic alterations of the somatostatinergic system revealed that an increased presence of functional SST2 receptor protected against retinal ischemia [11]. SST2 analogues might be of therapeutic benefit in retinal diseases [12,13,14]

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